Project Summary Scientific evidence continues to accumulate on the relation between obesity and asthma. More recent efforts are increasingly focused on the nature of the relation, as opposed to trying to determine whether such a relation exists. Many, although not all, epidemiological studies report a temporally correct and dose-response relationship between obesity and asthma. Animal studies support a causal link between the two disorders; however, the causal pathway remains to be understood in humans. In the new NIH asthma diagnosis and management guidelines, obesity is explicitly recognized, for the first time, as an important co-morbidity, and treatment of obesity is deemed to have potential benefits on asthma control based on limited studies. Although current evidence of the effects of weight loss on asthma outcomes is encouraging, it is far from being conclusive. The overall goal of the proposed randomized controlled trial (RCT) is to investigate the efficacy of an evidence-based lifestyle weight loss intervention on asthma control among obese adults. The intervention will involve a combination of dietary and physical activity changes and behavioral modification. This approach has demonstrated efficacy in preventing and controlling well-recognized obesity-related co- morbidities such as diabetes and hypertension. We will randomize 324 patients ages 18-70 years who have suboptimally controlled, persistent asthma and a body mass index of 30.0 to 39.9 kg/m2 from ~20,000 potentially eligible asthma patients at four medical centers of Kaiser Permanente in Northern California (KPNC), a large, group-model health maintenance organization. All participants will complete an office visit and a phone consultation, pre-randomization, with an on-site KPNC asthma care manager, and all will continue to receive KPNC standard of care from their physician post-randomization. Those randomly assigned to the experimental group will receive the comprehensive lifestyle weight loss intervention. The primary outcome will be the overall score at 12 months on the Juniper Asthma Control Questionnaire. The specific aims are to: 1) Determine whether the intervention improves measures of current impairment associated with asthma (asthma symptoms, spirometric lung function, activity limitations, rescue medication use, and asthma-related quality of life); 2) Determine whether the intervention improves measures of future risk associated with asthma (asthma exacerbations and adverse effects of asthma medication); 3) Examine potential mechanisms of intervention effects, focusing on the relative contributions of changes in weight, physical activity, and diet composition, after controlling for asthma medication potency and adherence; and 4) Explore potential effect modifiers, e.g. sex, race/ethnicity, education, and other baseline characteristics. This project will help advance current understanding of the nature of obesity-asthma relationship. If the weight loss intervention is proven to improve asthma outcomes, it will add to the other medical and environmental strategies available to manage asthma in obese adults, which may, in turn, lead to reduced morbidity and mortality associated with asthma and obesity. PUBLIC HEALTH RELEVANCE: Although the underlying mechanisms remain unclear, growing scientific evidence suggests that children and adults who are obese are at elevated risk of developing asthma or, for those who already have the disease, having worse symptoms. The new national asthma management guidelines recommend that clinicians consider advising asthma patients who are overweight or obese to lose weight, based on very limited studies showing that weight loss may improve asthma control, in addition to its other known health benefits. The current study aims to rigorously investigate whether weight loss, through recommended strategies for dietary modification, physical activity, and behavioral change, has significant clinical benefits for the management of asthma in obese adults. If successful, this project will help advance the current clinical guidelines for treating obese adults with asthma, which, in turn, may lead to reduced morbidity and mortality associated with asthma and obesity.